The objective of the proposed research is to a) establish a correlation between molecular defects in apolipoproteins and various human diseases which lead to premature atherosclerosis, and b) study in detail the molecular defects which underlie the existing apolipoprotein variations. The specific aims of the proposed study are: 1) To characterize the apoprotein isoproteins of subjects participating in a case control study risk factors of myocardia infarction. The apoproteins of the control group will be compared to the apoproteins of patients with myocardial infarctions. 2) To characterize the apoprotein isoproteins of patients with abnormalities of lipoprotein metabolism characterized as hyper or hypolipoproteinemias and compare them with the apoproteins of the control group study 1. The comparison of apoproteins of normal and diseased individuals will be done by two-dimensional gel electrohporesis and protein chemistry techniques. Both techniques are performed on a large scale by us. 3) To utilize existing and develop new molecular probes for human apolipoprotein genes. These probes will be used a) to screen for apolipoprotein gene variants by restriction analysis of genomic DNA using the blotting techniques of Southern, b) to isolate and sequence important apolipoprotein gene variants that will result from studies 1 and 2. Isolation and characterization of normal and variant apolipoprotein genes will be done by established recombinant DNA techniques currently in use in our laboratory. The findings of the proposed studies would be very important from a public health standpoint. Heart disease is at the present time the number one cause of death in the United States. Abnormalities in lipoprotein metabolism contribute significantly to coronary atherosclerosis and heart disease. The development of atherosclerosis could be retarded if the molecular bases of the disease which lead to it were known and tests were available to diagnose these diseases early in life. The proposed research intends to fulfill this goal. If we find an association between a human disease and an abnormality in a particular apolipoprotein or apolipoprotein gene, then the abnormal apolipoprotein or apolipoprotein gene might serve as a molecular marker for early diagnosis and treatment of the disease.